Background:

Based on in vitro and animal studies, certain cytokines and chemokines such as tissue factor (TF), vascular endothelial growth factor (VEGF), soluble (s) E-selectin (sE-sel), and tumor necrosis factor (TNF)-a have been shown to be associated with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Here we examined the levels of cytokines/chemokines in aPL-positive patients with or without SLE, and compared them to controls.

Methods:

Baseline sera/plasma of persistently aPL-positive patients [IgG/M Anticardiolipin antibody (aCL) > 40U, IgG/M anti-b2 glycoprotein-I antibody (ab2GPI) > 20U, and/or positive lupus anticoagulant test] were obtained from an ongoing pilot interventional clinical study (clinical trials. gov #: NCT00674297). The biomarker levels of these 22 aPL-positive patients (primary APS: 8, APS with SLE: 8, asymptomatic aPL without SLE: 4 and asymptomatic aPL with SLE: 2) were compared to 22 matched healthy controls with no evidence of autoimmune, infectious, or inflammatory diseases. Interleukin (IL)-1b, IL6, IL8, TNF-a, VEGF, interferon inducible protein (IP)-10 and sCD40L were measured in serum using a Multiplex Assay (Millipore Milliplex); titers of sE-sel, and sTF were detected by ELISA. The Kruskal-Wallis test was used to compare the levels of biomarkers in aPL-positive subjects as compared to the controls. Spearman test was used to correlate the levels of the biomarkers in the different subgroups of patients.

Results:

As compared to controls, we found an increase in the levels of IL-1b, IL6, TNF- a, IP-10, sCD40L and sTF in patients with APS. In a subgroup analysis, patients with aPL/APS and SLE (n=10) had significantly higher levels of TNF-a, IP10 and sCD40L as compared to aPL/APS patients without SLE (n=12) (p= 0.05, 0.029 and 0.05, respectively).

Biomarker

# Of aPL (+) samples elevated above cut-off points/(%)

Means of aPL positive samples

Means of controls

p

IL1b

16/22 (73)

7.65

0.35

<0.0001

IL6

17/22 (77)

42.15

0.71

<0.0001

IL8

9/22 (41)

27.44

40.87

0.1763

TNF-a

22/22 (100)

14.71

0.46

<0.0001

VEGF

12/22 (54)

208.78

113.59

0.9778

IP-10

22/22 (100)

683.43

106.7

<0.0001

sCD40L

21/22 (95)

1070.19

24.67

<0.0001

s TF

16/16 (100)

449.59

13.05

<0.0001

sE-sel

3/16 (19)

20.78

42.04

0.0006

Conclusions:

Our results underscore the importance of biomarkers in aPL-positive patients. This may help better understand the pathogenic mechanisms involved, and the development of targeted treatments.